Catalpol has been found to provide antioxidant and neuroprotective effects on mouse models of depression, improving their depressive behavior by upregulating the PI3K/Akt/Nrf2/HO-1 signaling pathway, indicating that this pathway could be used as a potential target and biomarker for the treatment of depression with catalpol (Wang et al., 2021a; Wu et al., 2021). This evidence concerns the gene NFE2L2 and major depressive disorder.